The gene coding for the entire extracellular domain of the IFN-alpha receptor (lacking the signal peptide) has been cloned in plasmid pGEX-2T and expressed in E. coli DH5 as a fusion protein with bacterial glutathione-S-transferase. A DNA fragment encoding amino acids 28-437 of the receptor protein was inserted into vector pGEX-2T at the EcoRI and BamHJ sites. A stop codon immediately downstream of the receptor sequence was added. Expression was induced by IPTG and the fusion protein was partially purified by gel chromatography on Sepharyl P S-300 followed by glutathione agarose affinity chromatography. Work is in progress to recover the non-fused receptor after-protease cleavage by thrombin, and to initiate studies on the physico chemical and biological characterization of the recombinant protein; antisera against the receptor will be produced and will be used to purify the natural protein from mammalian cells, and will serve as a probe to study the mechanisms of signal transduction involving interferon-alpha and its receptor(s).